Patterns of Sleep Restriction and Recovery: the Inflammatory Resolution Pathways
Overview
- Phase
- Early Phase 1
- Intervention
- Aspirin
- Conditions
- Inflammatory Response
- Sponsor
- Beth Israel Deaconess Medical Center
- Enrollment
- 66
- Locations
- 1
- Primary Endpoint
- Inflammatory Resolution Markers
- Status
- Active, not recruiting
- Last Updated
- last year
Overview
Brief Summary
Goal of this project is to investigate whether increases in inflammation that result from common patterns of restricting sleep on week nights and catching up on sleep over the weekend are caused by disruption in the newly discovered inflammatory resolution pathways. These pathways are crucial in the active termination of the inflammatory response, and their disruption may contribute to ongoing unresolved inflammation, which has been observed not only during periods of sleep restriction, but also after recovery sleep has been obtained. If the hypothesis is true, it is possible that increasing the body's natural production of endogenous, inflammatory resolution mediators may provide a non-behavioral strategy to limit the inflammatory consequences in those undergoing periods of sleep restriction with intermittent recovery sleep.
Detailed Description
Low-grade or unresolved inflammation is involved in the pathogenesis of many human diseases. Common sleep patterns of restricting sleep during the work week and "catching up" on sleep over the weekend lead to inflammatory upregulation that does not recover completely after the weekend. The goal of this proposal is to investigate, for the first time, inflammatory resolution pathways. Inflammatory resolution mediators, such as resolvins, are derived from omega-3 free fatty acids and actively 'turn-off' inflammation. Based on preliminary data, the investigators hypothesize that common sleep restriction-recovery patterns disrupt inflammatory resolution pathways, making it difficult to return to inflammatory homeostasis. If true, pharmacologically increasing the body's natural production of endogenous inflammatory resolution mediators may provide a way to reduce the detrimental inflammatory consequences of common sleep restriction-recovery patterns. The hypothesis will be tested using an experimental model that mimics common patterns of restricting sleep on weekdays and "catching up" on sleep on the weekend. The proposal will further utilize the unique ability of low-dose aspirin, which - like no other non-steroidal anti-inflammatory drug - is able to activate inflammatory resolution pathways. Healthy women and men between the ages of 18 to 65 years will be tested under three, 11-day in-hospital stays, during which participants will be exposed to control sleep or common patterns of sleep restriction-recovery. The three in-hospital stays will be combined with preemptive administration of low-dose aspirin or a placebo. Targeting inflammatory resolution pathways could provide a novel, non-behavioral strategy to mitigate both inflammatory consequences and future disease risks in those undergoing periods of sleep restriction-recovery patterns - a behavior pattern that is unlikely to be eradicated in the near future, as changes in sleep are generally difficult to make and to maintain.
Investigators
Monika Haack
Associate Professor of Neurology
Beth Israel Deaconess Medical Center
Eligibility Criteria
Inclusion Criteria
- •Women and men between the ages 18-65 years.
- •Body mass index (BMI) between 18.5 and 35 kg/m
- •For female participants: No significant discomfort during pre-menses/menses.
- •Daily sleep duration between 7-9 hours, verified by electronic sleep diary data for two weeks.
- •Habitual sleep period must begin within one hour of 11:00pm (to ensure normal entrainment).
- •Negative toxicology screen, including: amphetamines, barbiturates, benzodiazepines, cocaine, opiates, and methadone. Toxicology screening will be performed as part of the screening lab tests; an outside lab toxicology screening will not suffice.
Exclusion Criteria
- •Active infection/disease.
- •Following blood chemistry values outside of the laboratory's normal range or the range specified below:
- •WBC (range: 2.0-10.0 K/uL)
- •Platelet count
- •Hematocrit in range
- •TSH outside of the laboratory's normal range
- •Bilirubin \>1.5 upper limit of normal
- •ALT or AST \>2.5 upper limit of normal
- •Stage 4 chronic kidney disease based on CKD epi-equation
- •Pre-diabetes or diabetes (HbA1c \>5.7%)
Arms & Interventions
Control Sleep/Non-Active Placebo or 81mg Aspirin Pill
Daily intake of pill at bedtime over 2-week period prior to and during the 11-day in-hospital stay
Intervention: Aspirin
Control Sleep/Non-Active Placebo or 81mg Aspirin Pill
Daily intake of pill at bedtime over 2-week period prior to and during the 11-day in-hospital stay
Intervention: Placebo
Sleep Restriction/81mg Aspirin Pill
Daily intake of pill at bedtime over 2-week period prior to and during the 11-day in-hospital stay
Intervention: Aspirin
Sleep Restriction/Non-Active Placebo
Daily intake of pill at bedtime over 2-week period prior to and during the 11-day in-hospital stay
Intervention: Placebo
Outcomes
Primary Outcomes
Inflammatory Resolution Markers
Time Frame: Change from baseline to sleep restriction, single measure in the morning
Resolvins
Secondary Outcomes
- Inflammatory Markers(Change from baseline to sleep restriction, single measure in the morning)